Host Institution (HI)BIOSENSE INSTITUTE - RESEARCH AND DEVELOPMENT INSTITUTE FOR INFORMATION TECHNOLOGIES IN BIOSYSTEMS

Call DetailsStarting Grant (StG), SH6, ERC-2014-STG

SummaryThe BIRTH project will investigate the key biological and cultural mechanisms affecting fertility rates resulting the Neolithic Demogaphic Transition, the major demographic shift in human evolution. We integrate skeletal markers with micro-nutritional and macro-scaled cultural effects on fertility rates during the Early-Middle Holocene (10000-5000 BC) in the Central Balkans. Human, animal and plant remains, will be analysed using methods from bioarchaeological, forensic, chemical sciences in order to: 1) Investigate variability in the pattern of birth rates (number of pregnancies, interval(s) between them and the duration of the reproductive period) through histological analysis of irregularities in tooth cementum of women; 2) Determine paleoobstetric and neonatal body characteristics, health status and nutrition through analysis of skeletal remains; 3) Determine micronutritional changes during the Early-Middle Holocene through trace element (Zn, Ca and Fe) analysis; 4) Investigate the micro and macronutritional value of prehistoric foodstuffs, through an analysis of animal and plant remains and to compare the nutritional intake in relation to health and fertility; 5) Establish a chronology of the NDT in the Balkans by summed radiocarbon probability distributions; 6) Explore the possible role of culture in driving fertility increases, through analysis of community attitudes to birthing trough investigation of neonate graves and artifact connected to the birthing process. Given that the issues of health and fertility are of utmost importance in the present as they were in the past, the BIRTH project offers new understanding of biocultural mechanisms which led to fertility increase and novel approaches to ancient skeletal heritage, and emphasizes their great potential for modern humanity.

The BIRTH project will investigate the key biological and cultural mechanisms affecting fertility rates resulting the Neolithic Demogaphic Transition, the major demographic shift in human evolution. We integrate skeletal markers with micro-nutritional and macro-scaled cultural effects on fertility rates during the Early-Middle Holocene (10000-5000 BC) in the Central Balkans. Human, animal and plant remains, will be analysed using methods from bioarchaeological, forensic, chemical sciences in order to: 1) Investigate variability in the pattern of birth rates (number of pregnancies, interval(s) between them and the duration of the reproductive period) through histological analysis of irregularities in tooth cementum of women; 2) Determine paleoobstetric and neonatal body characteristics, health status and nutrition through analysis of skeletal remains; 3) Determine micronutritional changes during the Early-Middle Holocene through trace element (Zn, Ca and Fe) analysis; 4) Investigate the micro and macronutritional value of prehistoric foodstuffs, through an analysis of animal and plant remains and to compare the nutritional intake in relation to health and fertility; 5) Establish a chronology of the NDT in the Balkans by summed radiocarbon probability distributions; 6) Explore the possible role of culture in driving fertility increases, through analysis of community attitudes to birthing trough investigation of neonate graves and artifact connected to the birthing process. Given that the issues of health and fertility are of utmost importance in the present as they were in the past, the BIRTH project offers new understanding of biocultural mechanisms which led to fertility increase and novel approaches to ancient skeletal heritage, and emphasizes their great potential for modern humanity.

Max ERC Funding

1 714 880 €

Duration

Start date: 2015-10-01, End date: 2020-09-30

Project acronymCOOPAIRENT

ProjectCooper pairs as a source of entanglement

Researcher (PI)Szabolcs Csonka

Host Institution (HI)BUDAPESTI MUSZAKI ES GAZDASAGTUDOMANYI EGYETEM

Call DetailsStarting Grant (StG), PE3, ERC-2010-StG_20091028

SummaryEntanglement and non-locality are spectacular fundamentals of quantum mechanics and basic resources of future quantum computation algorithms. Electronic entanglement has attracted increasing attention during the last years. The electron spin as a purely quantum mechanical two level system has been put forward as a promising candidate for storing quantum information in solid state. Recently, great progress has been achieved in manipulation and read-out of quantum dot based spin Qubits. However, electron spin is also suitable to transfer quantum information, since mobile electrons can be coherently transmitted in a solid state device preserving the spin information. Thus, electron spin could provide a general platform for on-chip quantum computation and information processing.
Although several theoretical concepts have been worked out to address spin entangled mobile electrons, the absence of an entangler device has not allowed their realization so far. The aim of the present proposal is to overcome this experimental challenge and explore the entanglement of spatially separated electron pairs. Superconductors provide a natural source of entanglement, because their ground-state is composed of Cooper pairs in a spin-singlet state. However, the splitting of the Cooper pairs into separate electrons has to be enforced, which has been very recently realized by the applicant in two quantum dot Y-junction. This Y-junction will be used as a central building block to split Cooper pairs in a controlled fashion and the non-local nature of spin and charge correlations will be addressed in various device configurations.
Our research project will lead to a fundamental understanding of the production, manipulation and detection of spin entangled mobile electron pairs, thus it will significantly extend the frontiers of quantum coherence and opens a new horizon in the field of on-chip quantum information technologies.

Entanglement and non-locality are spectacular fundamentals of quantum mechanics and basic resources of future quantum computation algorithms. Electronic entanglement has attracted increasing attention during the last years. The electron spin as a purely quantum mechanical two level system has been put forward as a promising candidate for storing quantum information in solid state. Recently, great progress has been achieved in manipulation and read-out of quantum dot based spin Qubits. However, electron spin is also suitable to transfer quantum information, since mobile electrons can be coherently transmitted in a solid state device preserving the spin information. Thus, electron spin could provide a general platform for on-chip quantum computation and information processing.
Although several theoretical concepts have been worked out to address spin entangled mobile electrons, the absence of an entangler device has not allowed their realization so far. The aim of the present proposal is to overcome this experimental challenge and explore the entanglement of spatially separated electron pairs. Superconductors provide a natural source of entanglement, because their ground-state is composed of Cooper pairs in a spin-singlet state. However, the splitting of the Cooper pairs into separate electrons has to be enforced, which has been very recently realized by the applicant in two quantum dot Y-junction. This Y-junction will be used as a central building block to split Cooper pairs in a controlled fashion and the non-local nature of spin and charge correlations will be addressed in various device configurations.
Our research project will lead to a fundamental understanding of the production, manipulation and detection of spin entangled mobile electron pairs, thus it will significantly extend the frontiers of quantum coherence and opens a new horizon in the field of on-chip quantum information technologies.

Max ERC Funding

1 496 112 €

Duration

Start date: 2011-02-01, End date: 2016-10-31

Project acronymCROME

ProjectCrossed Memories, Politics of Silence: The Colonial-Liberation Wars in Postcolonial Times

Researcher (PI)Miguel Gonçalo CARDINA

Host Institution (HI)CENTRO DE ESTUDOS SOCIAIS

Call DetailsStarting Grant (StG), SH6, ERC-2016-STG

SummaryColonial-Liberation Wars generate plural memories, conflicting evocations and persisting amnesias. The project’s main challenge is to produce innovative knowledge about the memories of the wars fought by the Portuguese state and pro-independence African movements between 1961 and 1974/5. The approach chosen is simultaneously diachronic and comparative, inasmuch as it contrasts changes that took place between the end of the conflicts and nowadays, regarding how wars, colonial pasts and anticolonial legacies have been remembered and silenced in Portugal, Angola, Mozambique, Guinea-Bissau, Cape Verde and São Tomé and Principe. The key hypothesis is that wars - as pivotal moments that ended the cycle of Empire in Portugal and started the cycle of African independences in the former Portuguese colonies - triggered memorialisation and silencing processes which had their own historicity.
CROME is divided into two strands. The first one, named ‘Colonial Wars, Postcolonial States’, looks at the role played by the states under consideration in mobilising, articulating and recognising the past, but also in actively generating selective representations. ‘Memory as a battlefield’ is the second strand, which will highlight distinct uses of the past and dynamics between social memories and individual memories.
The project intends to demonstrate how wars gave rise to multiple memories and conflicting historical judgements, mostly in Portugal, but also to examine how the specific nature of the (post-)colonial histories of each African country has generated different ways to summon war memories and (anti-)colonial legacies. CROME will, thus, put forward a ground-breaking perspective in terms of colonial-liberation war studies, and will be instrumental in dealing with such traumatic experience, for its comparative approach might help overcoming everlasting constraints still at play today, caused by the historical burden European colonialism left behind.

Colonial-Liberation Wars generate plural memories, conflicting evocations and persisting amnesias. The project’s main challenge is to produce innovative knowledge about the memories of the wars fought by the Portuguese state and pro-independence African movements between 1961 and 1974/5. The approach chosen is simultaneously diachronic and comparative, inasmuch as it contrasts changes that took place between the end of the conflicts and nowadays, regarding how wars, colonial pasts and anticolonial legacies have been remembered and silenced in Portugal, Angola, Mozambique, Guinea-Bissau, Cape Verde and São Tomé and Principe. The key hypothesis is that wars - as pivotal moments that ended the cycle of Empire in Portugal and started the cycle of African independences in the former Portuguese colonies - triggered memorialisation and silencing processes which had their own historicity.
CROME is divided into two strands. The first one, named ‘Colonial Wars, Postcolonial States’, looks at the role played by the states under consideration in mobilising, articulating and recognising the past, but also in actively generating selective representations. ‘Memory as a battlefield’ is the second strand, which will highlight distinct uses of the past and dynamics between social memories and individual memories.
The project intends to demonstrate how wars gave rise to multiple memories and conflicting historical judgements, mostly in Portugal, but also to examine how the specific nature of the (post-)colonial histories of each African country has generated different ways to summon war memories and (anti-)colonial legacies. CROME will, thus, put forward a ground-breaking perspective in terms of colonial-liberation war studies, and will be instrumental in dealing with such traumatic experience, for its comparative approach might help overcoming everlasting constraints still at play today, caused by the historical burden European colonialism left behind.

SummaryDeep learning is revolutionizing the field of Natural Language Processing (NLP), with breakthroughs in machine translation, speech recognition, and question answering. New language interfaces (digital assistants, messenger apps, customer service bots) are emerging as the next technologies for seamless, multilingual communication among humans and machines.
From a machine learning perspective, many problems in NLP can be characterized as structured prediction: they involve predicting structurally rich and interdependent output variables. In spite of this, current neural NLP systems ignore the structural complexity of human language, relying on simplistic and error-prone greedy search procedures. This leads to serious mistakes in machine translation, such as words being dropped or named entities mistranslated. More broadly, neural networks are missing the key structural mechanisms for solving complex real-world tasks requiring deep reasoning.
This project attacks these fundamental problems by bringing together deep learning and structured prediction, with a highly disruptive and cross-disciplinary approach. First, I will endow neural networks with a "planning mechanism" to guide structural search, letting decoders learn the optimal order by which they should operate. This makes a bridge with reinforcement learning and combinatorial optimization. Second, I will develop new ways of automatically inducing latent structure inside the network, making it more expressive, scalable and interpretable. Synergies with probabilistic inference and sparse modeling techniques will be exploited. To complement these two innovations, I will investigate new ways of incorporating weak supervision to reduce the need for labeled data.
Three highly challenging applications will serve as testbeds: machine translation, quality estimation, and dependency parsing. To maximize technological impact, a collaboration is planned with a start-up company in the crowd-sourcing translation industry.

Deep learning is revolutionizing the field of Natural Language Processing (NLP), with breakthroughs in machine translation, speech recognition, and question answering. New language interfaces (digital assistants, messenger apps, customer service bots) are emerging as the next technologies for seamless, multilingual communication among humans and machines.
From a machine learning perspective, many problems in NLP can be characterized as structured prediction: they involve predicting structurally rich and interdependent output variables. In spite of this, current neural NLP systems ignore the structural complexity of human language, relying on simplistic and error-prone greedy search procedures. This leads to serious mistakes in machine translation, such as words being dropped or named entities mistranslated. More broadly, neural networks are missing the key structural mechanisms for solving complex real-world tasks requiring deep reasoning.
This project attacks these fundamental problems by bringing together deep learning and structured prediction, with a highly disruptive and cross-disciplinary approach. First, I will endow neural networks with a "planning mechanism" to guide structural search, letting decoders learn the optimal order by which they should operate. This makes a bridge with reinforcement learning and combinatorial optimization. Second, I will develop new ways of automatically inducing latent structure inside the network, making it more expressive, scalable and interpretable. Synergies with probabilistic inference and sparse modeling techniques will be exploited. To complement these two innovations, I will investigate new ways of incorporating weak supervision to reduce the need for labeled data.
Three highly challenging applications will serve as testbeds: machine translation, quality estimation, and dependency parsing. To maximize technological impact, a collaboration is planned with a start-up company in the crowd-sourcing translation industry.

Max ERC Funding

1 436 000 €

Duration

Start date: 2018-02-01, End date: 2023-01-31

Project acronymDEPENDABLECLOUD

ProjectTowards the dependable cloud:
Building the foundations for tomorrow's dependable cloud computing

SummaryCloud computing is being increasingly adopted by individuals, organizations, and governments. However, as the computations that are offloaded to the cloud expand to societal-critical services, the dependability requirements of cloud services become much higher, and we need to ensure that the infrastructure that supports these services is ready to meet these requirements. In particular, this proposal tackles the challenges that arise from two distinctive characteristic of the cloud infrastructure.
The first is that non-crash faults, despite being considered highly unlikely by the designers of traditional systems, become commonplace at the scale and complexity of the cloud infrastructure. We argue that the current ad-hoc methods for handling these faults are insufficient, and that the only principled approach of assuming Byzantine faults is too pessimistic. Therefore, we call for a new systematic approach to tolerating non-crash, non-adversarial faults. This requires the definition of a new fault model, and the construction of a series of building blocks and key protocol elements that enable the construction of fault-tolerant cloud services.
The second issue is that to meet their scalability requirements, cloud services spread their state across multiple data centers, and direct users to the closest one. This raises the issue that not all operations can be executed optimistically, without being aware of concurrent operations over the same data, and thus multiple levels of consistency must coexist. However, this puts the onus of reasoning about which behaviors are allowed under such a hybrid consistency model on the programmer of the service. We propose a systematic solution to this problem, which includes a novel consistency model that allows for developing highly scalable services that are fast when possible and consistent when necessary, and a labeling methodology to guide the programmer in deciding which operations can run at each consistency level.

Cloud computing is being increasingly adopted by individuals, organizations, and governments. However, as the computations that are offloaded to the cloud expand to societal-critical services, the dependability requirements of cloud services become much higher, and we need to ensure that the infrastructure that supports these services is ready to meet these requirements. In particular, this proposal tackles the challenges that arise from two distinctive characteristic of the cloud infrastructure.
The first is that non-crash faults, despite being considered highly unlikely by the designers of traditional systems, become commonplace at the scale and complexity of the cloud infrastructure. We argue that the current ad-hoc methods for handling these faults are insufficient, and that the only principled approach of assuming Byzantine faults is too pessimistic. Therefore, we call for a new systematic approach to tolerating non-crash, non-adversarial faults. This requires the definition of a new fault model, and the construction of a series of building blocks and key protocol elements that enable the construction of fault-tolerant cloud services.
The second issue is that to meet their scalability requirements, cloud services spread their state across multiple data centers, and direct users to the closest one. This raises the issue that not all operations can be executed optimistically, without being aware of concurrent operations over the same data, and thus multiple levels of consistency must coexist. However, this puts the onus of reasoning about which behaviors are allowed under such a hybrid consistency model on the programmer of the service. We propose a systematic solution to this problem, which includes a novel consistency model that allows for developing highly scalable services that are fast when possible and consistent when necessary, and a labeling methodology to guide the programmer in deciding which operations can run at each consistency level.

Max ERC Funding

1 076 084 €

Duration

Start date: 2012-10-01, End date: 2018-01-31

Project acronymDUNES

ProjectSea, Sand and People. An Environmental History of Coastal Dunes

Researcher (PI)Joana FREITAS

Host Institution (HI)Faculdade de letras da Universidade de Lisboa

Call DetailsStarting Grant (StG), SH6, ERC-2018-STG

SummaryDunes are now protected environments, being top priority for coastal managers, because of their important role as coastal defences. But, it was not like that in the past.
For centuries dunes were considered unproductive and dangerous. The sand blown by the wind was taken inland, invading fields, silting rivers and destroying villages. In the eighteenth century, a strategy was developed to fight against the dunes: trapping them with trees, with the double purpose of preventing the destruction of arable land and increasing their economic value converting them into forest areas. Different governments, in different countries supported the immobilization of the shifting sands. The strategy, developed in Europe, was taken to other places in the world. These works caused profound changes in vast coastal areas transforming arid landscapes of sandy dunes into green tree forests.
This project aims to explore human-environment relations in coastal areas worldwide, since the eighteenth century until today, through the study of dunes as hybrid landscapes. Based on selected case-studies and comparative approaches, the project will focus on the origins, reasons and means of dunes afforestation; the impacts of the creation of new landscapes to local communities and ecosystems; and the present situation of dunes as coastal defences and rehabilitated environments. The final purpose is to produce an innovative global history of coastal dunes, combining knowledges from both Humanities and Social Sciences and Physical and Life Sciences, which has never been done.
Supported by an interdisciplinary team, this research will result in new developments in the field of the Environmental History studies; provide relevant knowledge considering the need of efficient management solutions to adapt to the expected mean sea level rise; and stimulate environmental citizenship by disseminating the idea that the future of the world coasts depends on today’s actions.

Dunes are now protected environments, being top priority for coastal managers, because of their important role as coastal defences. But, it was not like that in the past.
For centuries dunes were considered unproductive and dangerous. The sand blown by the wind was taken inland, invading fields, silting rivers and destroying villages. In the eighteenth century, a strategy was developed to fight against the dunes: trapping them with trees, with the double purpose of preventing the destruction of arable land and increasing their economic value converting them into forest areas. Different governments, in different countries supported the immobilization of the shifting sands. The strategy, developed in Europe, was taken to other places in the world. These works caused profound changes in vast coastal areas transforming arid landscapes of sandy dunes into green tree forests.
This project aims to explore human-environment relations in coastal areas worldwide, since the eighteenth century until today, through the study of dunes as hybrid landscapes. Based on selected case-studies and comparative approaches, the project will focus on the origins, reasons and means of dunes afforestation; the impacts of the creation of new landscapes to local communities and ecosystems; and the present situation of dunes as coastal defences and rehabilitated environments. The final purpose is to produce an innovative global history of coastal dunes, combining knowledges from both Humanities and Social Sciences and Physical and Life Sciences, which has never been done.
Supported by an interdisciplinary team, this research will result in new developments in the field of the Environmental History studies; provide relevant knowledge considering the need of efficient management solutions to adapt to the expected mean sea level rise; and stimulate environmental citizenship by disseminating the idea that the future of the world coasts depends on today’s actions.

SummaryThe aim of this project is to develop and analyse infinite dimensional dynamical models for the transmission dynamics and propagation of infectious diseases. We use an integrated approach which spans from the abstract theory of functional differential equations to the practical problems of epidemiology, with serious implications to public health policy, prevention, control and mitigation strategies in cases such as the ongoing battle against the nascent H1N1 pandemic.
Delay differential equations are one of the most powerful mathematical modeling tools and they arise naturally in various applications from life sciences to engineering and physics, whenever temporal delays are important. In abstract terms, functional differential equations describe dynamical systems, when their evolution depends on the solution at prior times.
The central theme of this project is to forge strong links between the abstract theory of delay differential equations and practical aspects of epidemiology. Our research will combine competencies in different fields of mathematics and embrace theoretical issues as well as real life applications.
In particular, the theory of equations with state dependent delays is extremely challenging, and this field is at present on the verge of a breakthrough. Developing new theories in this area and connecting them to relevant applications would go far beyond the current research frontier of mathematical epidemiology and could open a new chapter in disease modeling.

The aim of this project is to develop and analyse infinite dimensional dynamical models for the transmission dynamics and propagation of infectious diseases. We use an integrated approach which spans from the abstract theory of functional differential equations to the practical problems of epidemiology, with serious implications to public health policy, prevention, control and mitigation strategies in cases such as the ongoing battle against the nascent H1N1 pandemic.
Delay differential equations are one of the most powerful mathematical modeling tools and they arise naturally in various applications from life sciences to engineering and physics, whenever temporal delays are important. In abstract terms, functional differential equations describe dynamical systems, when their evolution depends on the solution at prior times.
The central theme of this project is to forge strong links between the abstract theory of delay differential equations and practical aspects of epidemiology. Our research will combine competencies in different fields of mathematics and embrace theoretical issues as well as real life applications.
In particular, the theory of equations with state dependent delays is extremely challenging, and this field is at present on the verge of a breakthrough. Developing new theories in this area and connecting them to relevant applications would go far beyond the current research frontier of mathematical epidemiology and could open a new chapter in disease modeling.

Max ERC Funding

796 800 €

Duration

Start date: 2011-05-01, End date: 2016-12-31

Project acronymEVOLOR

ProjectCognitive Ageing in Dogs

Researcher (PI)Eniko Kubinyi

Host Institution (HI)EOTVOS LORAND TUDOMANYEGYETEM

Call DetailsStarting Grant (StG), LS9, ERC-2015-STG

SummaryThe aim of this project is to understand the causal factors contributing to the cognitive decline during senescence and to develop sensitive and standardized behaviour tests for early detection in order to increase the welfare of affected species. With the rapidly ageing population of Europe, related research is a priority in the European Union.
We will focus both on characterising the ageing phenotype and the underlying biological processes in dogs as a well-established natural animal model. We develop a reliable and valid test battery applying innovative multidisciplinary methods (e.g. eye-tracking, motion path analysis, identification of behaviour using inertial sensors, EEG, fMRI, candidate gene, and epigenetics) in both longitudinal and cross-sectional studies. We expect to reveal specific environmental risk factors which hasten ageing and also protective factors which may postpone it. We aim to provide objective criteria (behavioural, physiological and genetic biomarkers) to assess and predict the ageing trajectory for specific individual dogs. This would help veterinarians to recognise the symptoms early, and initiate necessary counter actions.
This approach establishes the framework for answering the broad question that how we can extend the healthy life of ageing dogs which indirectly also contributes to the welfare of the owner and decreases veterinary expenses. The detailed description of the ageing phenotype may also facilitate the use of dogs as a natural model for human senescence, including the development and application of pharmaceutical interventions.
We expect that our approach offers the scientific foundation to delay the onset of cognitive ageing in dog populations by 1-2 years, and also increase the proportion of dogs that enjoy healthy ageing.

The aim of this project is to understand the causal factors contributing to the cognitive decline during senescence and to develop sensitive and standardized behaviour tests for early detection in order to increase the welfare of affected species. With the rapidly ageing population of Europe, related research is a priority in the European Union.
We will focus both on characterising the ageing phenotype and the underlying biological processes in dogs as a well-established natural animal model. We develop a reliable and valid test battery applying innovative multidisciplinary methods (e.g. eye-tracking, motion path analysis, identification of behaviour using inertial sensors, EEG, fMRI, candidate gene, and epigenetics) in both longitudinal and cross-sectional studies. We expect to reveal specific environmental risk factors which hasten ageing and also protective factors which may postpone it. We aim to provide objective criteria (behavioural, physiological and genetic biomarkers) to assess and predict the ageing trajectory for specific individual dogs. This would help veterinarians to recognise the symptoms early, and initiate necessary counter actions.
This approach establishes the framework for answering the broad question that how we can extend the healthy life of ageing dogs which indirectly also contributes to the welfare of the owner and decreases veterinary expenses. The detailed description of the ageing phenotype may also facilitate the use of dogs as a natural model for human senescence, including the development and application of pharmaceutical interventions.
We expect that our approach offers the scientific foundation to delay the onset of cognitive ageing in dog populations by 1-2 years, and also increase the proportion of dogs that enjoy healthy ageing.

Max ERC Funding

1 202 500 €

Duration

Start date: 2016-06-01, End date: 2021-05-31

Project acronymGelGeneCircuit

ProjectCancer heterogeneity and therapy profiling using bioresponsive nanohydrogels for the delivery of multicolor logic genetic circuits.

Researcher (PI)João CONDE

Host Institution (HI)UNIVERSIDADE NOVA DE LISBOA

Call DetailsStarting Grant (StG), LS9, ERC-2019-STG

SummaryConventional cancer therapies suffer from poor efficacy owing to the lack of efficient delivery systems and to the inherent tumor heterogeneity that requires multi-modal approach to abrogate cancer progression. Nanotechnology holds promise to address these drawbacks, as the use of (bio)nanomaterials for diagnostics and therapy has been gaining momentum over the last years. The main goal of this project is to develop a novel and facile platform capable of profiling both the therapy outcome and heterogeneity in cancer, by using bioresponsive nanohydrogels for the delivery of logic multicolor synthetic gene circuits. These logic synthetic gene circuits will be designed as a biobarcode of multicolor RNA circuits embedded in hybrid nanoparticles and doped in hydrogels for local therapy in breast cancer in vivo. Using cell-type specific promoters, the multicolor miRNA circuits will be expressed specifically to each type of the cells of the tumor microenvironment. Subsequently, this will permit to evaluate the therapeutic efficacy in a cell-by-cell basis and to profile the tumor heterogeneity across different breast cancer types. In order to potentiate the translation of this ground-breaking platform into clinics and precision medicine, novel de-regulated miRNA targets will be identified based on screens performed in breast cancer patient-derived tumors that better reflect the heterogeneous tumor microenvironment in a patient-by-patient basis.
In sum, the material platforms developed herein and newly identified biological targets can be harnessed to design effective cancer treatments that go beyond breast cancer. The project is highly versatile and multidisciplinary and this system can be easily adapted to target any cancer cell type and molecular mechanisms and translated to clinical testing.

Conventional cancer therapies suffer from poor efficacy owing to the lack of efficient delivery systems and to the inherent tumor heterogeneity that requires multi-modal approach to abrogate cancer progression. Nanotechnology holds promise to address these drawbacks, as the use of (bio)nanomaterials for diagnostics and therapy has been gaining momentum over the last years. The main goal of this project is to develop a novel and facile platform capable of profiling both the therapy outcome and heterogeneity in cancer, by using bioresponsive nanohydrogels for the delivery of logic multicolor synthetic gene circuits. These logic synthetic gene circuits will be designed as a biobarcode of multicolor RNA circuits embedded in hybrid nanoparticles and doped in hydrogels for local therapy in breast cancer in vivo. Using cell-type specific promoters, the multicolor miRNA circuits will be expressed specifically to each type of the cells of the tumor microenvironment. Subsequently, this will permit to evaluate the therapeutic efficacy in a cell-by-cell basis and to profile the tumor heterogeneity across different breast cancer types. In order to potentiate the translation of this ground-breaking platform into clinics and precision medicine, novel de-regulated miRNA targets will be identified based on screens performed in breast cancer patient-derived tumors that better reflect the heterogeneous tumor microenvironment in a patient-by-patient basis.
In sum, the material platforms developed herein and newly identified biological targets can be harnessed to design effective cancer treatments that go beyond breast cancer. The project is highly versatile and multidisciplinary and this system can be easily adapted to target any cancer cell type and molecular mechanisms and translated to clinical testing.

SummaryA classical problem in the field of interacting particle systems (IPS) is to derive the macroscopic laws of the thermodynamical quantities of a physical system by considering an underlying microscopic dynamics which is composed of particles that move according to some prescribed stochastic, or deterministic, law. The macroscopic laws can be partial differential equations (PDE) or stochastic PDE (SPDE) depending on whether one is looking at the convergence to the mean or to the fluctuations around that mean. One of the purposes of this research project is to give a mathematically rigorous description of the derivation of SPDE from different IPS. We will focus on the derivation of the stochastic Burgers equation (SBE) and its integrated counterpart, namely, the KPZ equation, as well as their fractional versions. The KPZ equation is conjectured to be a universal SPDE describing the fluctuations of randomly growing interfaces of 1d stochastic dynamics close to a stationary state. With this study we want to characterize what is known as the KPZ universality class: the weak and strong conjectures. The latter states that there exists a universal process, namely the KPZ fixed point, which is a fixed point of the renormalization group operator of space-time scaling 1:2:3, for which the KPZ is also invariant. The former states that the fluctuations of a large class of 1d conservative microscopic dynamics are ruled by stationary solutions of the KPZ. Our goal is threefold: first, to derive the KPZ equation from general weakly asymmetric systems, showing its universality; second, to derive new SPDE, which are less studied in the literature, as the fractional KPZ from IPS which allow long jumps, the KPZ with boundary conditions from IPS in contact with reservoirs or with defects, and coupled KPZ from IPS with more than one conserved quantity. Finally, we will analyze the fluctuations of purely strong asymmetric systems, which are conjectured to be given by the KPZ fixed point.

A classical problem in the field of interacting particle systems (IPS) is to derive the macroscopic laws of the thermodynamical quantities of a physical system by considering an underlying microscopic dynamics which is composed of particles that move according to some prescribed stochastic, or deterministic, law. The macroscopic laws can be partial differential equations (PDE) or stochastic PDE (SPDE) depending on whether one is looking at the convergence to the mean or to the fluctuations around that mean. One of the purposes of this research project is to give a mathematically rigorous description of the derivation of SPDE from different IPS. We will focus on the derivation of the stochastic Burgers equation (SBE) and its integrated counterpart, namely, the KPZ equation, as well as their fractional versions. The KPZ equation is conjectured to be a universal SPDE describing the fluctuations of randomly growing interfaces of 1d stochastic dynamics close to a stationary state. With this study we want to characterize what is known as the KPZ universality class: the weak and strong conjectures. The latter states that there exists a universal process, namely the KPZ fixed point, which is a fixed point of the renormalization group operator of space-time scaling 1:2:3, for which the KPZ is also invariant. The former states that the fluctuations of a large class of 1d conservative microscopic dynamics are ruled by stationary solutions of the KPZ. Our goal is threefold: first, to derive the KPZ equation from general weakly asymmetric systems, showing its universality; second, to derive new SPDE, which are less studied in the literature, as the fractional KPZ from IPS which allow long jumps, the KPZ with boundary conditions from IPS in contact with reservoirs or with defects, and coupled KPZ from IPS with more than one conserved quantity. Finally, we will analyze the fluctuations of purely strong asymmetric systems, which are conjectured to be given by the KPZ fixed point.